Proximal tubule potassium reabsorption

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

Proximal tubule Cells of the PCT are responsible for bulk transport of solutes, with approximately 70-80% of the filtered load of sodium chloride (active processes) and water (passive, down the osmotic gradient established by sodium reabsorption) and essentially all of the amino acids, bicarbonate, glucose and potassium being reabsorbed in this region. 

Carbonic anhydrase influences the tubular reabsorption of sodium in proximal tubule where biocarbonate absorption occurs and in the distal tubule where sodium is exchanged for potassium or hydrogen ion and bicarbonate is formed as the accompanying anion. The hydration of carbon dioxide takes place under the influence of enzyme carbonic anhydrase which forms carbonic acid which dissociates and breaks into hydrogen and carbonate ions. 

Hypercalcemia can be a medical emergency. Because loop diuretics reduce Ca2+ reabsorption significantly, they can be quite effective in promoting Ca2+ diuresis. However, loop diuretics alone can cause marked volume contraction. If this occurs, loop diuretics are ineffective (and potentially counterproductive) because Ca2+ reabsorption in the proximal tubule would be enhanced. Thus, saline must be administered simultaneously with loop diuretics if an effective Ca2+ diuresis is to be maintained. The usual approach is to infuse normal saline and furosemide (80-120 mg) intravenously. Once the diuresis begins, the rate of saline infusion can be matched with the urine flow rate to avoid volume depletion. Potassium chloride may be added to the saline infusion as needed. 

Cell death due to apoptosis or necrosis is not the only form of tubular injury in AKI. There is also sub-lethal injury causing cell dysfunction. For example, alterations in proximal tubular cell polarity occur during renal ischemia. Tubule polarity is essential for its primary function of selective reabsorption of ions from the tubular fluid. Sodium-potassium-ATPase (NaK-ATPase), the enzyme, normally localized to the basolateral membrane, maintains tubular polarity by regulation of cellular transport sodium and potassium in proximal tubules. NaK-ATPase is hnked to the cytoskeleton/ membrane complex by a variety of proteins including spectrin. It has been demonstrated that in early reperfusion period spectrin dissociates from the cytosleleton and NaK-ATPase moves from the basolateral membrane into the cytoplasm and apical membrane [54-58]. 

Lithium is also known to interact in a variety of ways with different classes of diuretic drugs. Thiazide diuretics increase serum lithium concentration by increasing reabsorption of lithium, along with that of sodium, in the proximal tubule. With potassium-sparing diuretics, conflicting results have been reported. Increased serum lithium concentrations may be seen after amiloride. However, the loop diuretic furosemide safely can be combined with lithium with no reduction in renal lithium clearance or consequent increase in serum lithium concentration (191, 192). Other diuretics, for example, carbonic anhydrase inhibitor and xanthine derivatives, decrease serum... 

The proximal tubule is the most metabolically active part of the nephron, facilitating the reabsorption of 60% to 80% of the glomerular filtrate volume—including 70% of the filtered load of sodium and chloride, most of the potassium, glucose, bicarbonate, phosphate, and sulfate—and secreting 90% of the hydrogen ion excreted by the kidney (Table 45-1). 

General. Noteworthy reports- and reviews pertaining to the pharma-cologicalj endocrinological > and clinical aspects of diuretics have appeared in the recent literature. The use of diuretics in the treatment of hypertension has been reviewed with especial emphasis on the hypotensive action of the aldosterone antagonist, spironolactone.° Fundamental studies on the mechanism of transport of electrolyte across the tubular epithelium have indicated that phospholipids may play a critical role. Phospholipase C and pancreatic lipase markedly reduced the rate of reabsorption of saline droplets infused into rat proximal tubules. Likewise, phospholipase C reduced the ability of extractable lipids to bind sodium and potassium ions in rat kidney homogenates whereas, phospholipase D and ribonuclease appear to enhance cation binding. ... 

In type II renal tubular acidosis there is a defect in the secretion of hydrogen ions by the proximal tubule. Because the proximal tubule is the major site of bicarbonate reabsorption (4000 mEq of bicarbonate per day as compared to 70 mEq in the distal tubule), the defect in secretion of hydrogen ions in this condition leads to the flooding of the distal tubule with bicarbonate. The capacity of hydrogen ions secreted by the distal tubule to buffer this massive efflux of bicarbonate is soon overwhelmed and, as a result, large quantities of bicarbonate are excreted in the urine. Much more bicarbonate needs to be administered in this condition to correct the acidosis than is necessary in type I renal tubular acidosis. In general, in renal tubular acidosis the impairment in hydrogen ion secretion leads to excretion of potassium ions in urine. 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

The mechanism of action of the benzothiadiazine diuretics is primarily related to their ability to inhibit the Na /cr symporter located in the distal convoluted tubule. These diuretics are actively secreted in the proximal tubule and are carried to the loop of Henie and to the distal tubule. The major site of action of these compounds is in the distal tubule, where these drugs compete for the chloride binding site of the Na /cr symporter and inhibit the reabsorption of sodium and chloride ions. For this reason, they are referred to as saluretics. They also inhibit the reabsorption of potassium and bicarbonate ions, but to a lesser degree. 

A microcapillary version of the potassium liquid ion-exchanger electrode has been used in situ for following potassium ion gradients along the proximal convoluted tubule of a rat kidney [281]. The mean tubular fluid to plasma potassium ion concentration ratio falls significantly from 0.89 for the first convolution to 0.81 for the last convolution of the proximal tubule. Such a disproportionate reabsorption of potassium does not support a common cationic pump mechanism whereby ions and water are reabsorbed in the same proportion as they are first delivered as in the case of sodium [281]. 

The mechanism regulating sodium reabsorption in the proximal tubules is still debated. Ten to fifteen per cent of the filtered sodium load is reabsorbed in the distal tubule. This reabsorption is no longer isotonic but occurs against a concentration gradient (from low concentration in urine toward high concentration in interstitial tissue). Moreover, only part of the sodium reabsorption is accompanied by cation absorption. The electrolytic balance is maintained in part by replacing sodium with potassium, hydrogen, and ammonium ions. 

Potassium (K" ) is the major intracellular electrolyte and its concentration in the body is regulated by the kidney although corrections of disturbances in potassium balance require several hours (Giebisch 1998). Whereas a marked decrease is required (20-40 %) to induce reabsorption in the kidney, an increase results in a prompt rise in clearance. The reabsorption of most occurs in the proximal tubule by passive transport, while secretion (active and passive) occurs in the distal tubule and collecting ducts. However, depending on body needs, secretion can be replaced by reabsorption. 

This is consistent with the fact that in Necturus the proximal tubule does not modify the filtered potassium load. There is no significant net transport, reabsorptive or secretory, in the Necturus proximal tubule. The observed electrical asymmetry of this epithelium may be due to the difference in magnitude of two K" " diffusion potentials in series. Thus the simultaneously observed activity distribution ratios can account for all the electrical asjmimetry without the need to invoke a significant effect of passive leak of Na" " on either membrane boundary. 

While sodium reabsorption in the distal nephron, influenced by aldosterone, is particularly important because it can produce sodium-free urine and promote potassium loss, the great majority of renal sodium reabsorption occurs elsewhere about 25% in the loop of Henle and most in the proximal tubule. The loop is also a main site of magnesium reabsorption, hence the tendency for loop diuretics to cause hypomagnesemia. 

Apical membrane Na+/H+ exchange (via NHE3) and bicarbonate reabsorption in the proximal convoluted tubule cell. Na+/K+ ATPase is present in the basolateral membrane to maintain intracellular sodium and potassium levels within the normal range. Because of rapid equilibration, concentrations of the solutes are approximately equal in the interstitial fluid and the blood. Carbonic anhydrase (CA) is found in other locations in addition to the brush border of the luminal membrane. 

---